crossing96/oncoscreening huggingface dataset:
CD3 high and FoxP3 - tumor-infiltrating lymphocytes in the invasive margin as a favorable prognostic marker in patients with invasive urothelial carcinoma of the bladder.	Tumor-infiltrating lymphocytes (TILs) have been extensively explored as prognostic biomarkers and cellular immunotherapy methods in cancer patients. However, the prognostic significance of TILs in bladder cancer remains unresolved. We evaluated the prognostic effect of TILs in bladder cancer patients. Sixty-four bladder cancer patients who underwent surgical resection between 2018 and 2020 in Zhejiang Provincial People's Hospital were analyzed in this study. Immunohistochemistry was used to evaluate CD3, CD4, CD8, and FoxP3 expression on TILs in the invasive margin of tumor tissue, and the presence of TIL subsets was correlated with the disease-free survival (DFS) of bladder cancer patients. The relationship between clinical-pathological features and DFS were analyzed. A high level of CD3 + TILs (CD3 high TILs) ( P  = 0.027) or negative expression of FoxP3 TILs (FoxP3 - TILs) ( P  = 0.016) was significantly related to better DFS in bladder cancer patients. Those with CD3 high FoxP3 - TILs had the best prognosis compared to those with CD3 high FoxP3 + TILs or CD3 low FoxP3 - TILs ( P  = 0.0035). Advanced age [HR 4.57, (1.86-11.25); P  = 0.001], CD3 low TILs [HR 0.21, (0.06-0.71); P  = 0.012], CD8 low TILs [HR 0.34, (0.12-0.94); P = 0.039], and FoxP3 + TILs [HR 10.11 (1.96-52.27); P  = 0.006] in the invasive margin were associated with a worse prognosis (DFS) by multivariate analysis. In conclusion, we demonstrated that CD3 high , FoxP3 - , and CD3 high FoxP3 - TILs in the invasive margin were significantly associated with better DFS. CD8 high and CD4 high TILs in the invasive margin tended to predict better DFS in bladder cancer. Patients with CD4 high CD8 high TILs in the invasive margin were likely to have a better prognosis.	bladder
Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients.	"Inflammatory cancer-associated fibroblasts (iCAFs) are closely related to progression, anticancer therapeutic resistance, and poor prognosis of bladder cancer (BCa). However, the functional role of iCAFs in BCa has been poorly studied. In our study, two BCa scRNA-seq datasets (GSE130001 and GSE146137) were obtained and integrated by the Seurat pipeline. Based on reported markers (COL1A1 and PDGFRA), iCAFs were identified and the related signature of 278 markers was developed. Following unsupervised consensus clustering, two molecular subtypes of TCGA-BLCA were identified and characterized by distinct dysregulated cancer hallmarks, immunological tumor microenvironments, prognoses, responses to chemotherapy/immunotherapy, and stemness. Subsequently, the robustness of the signature-based clustering, in terms of prognosis and therapeutic response prediction, was validated in a GEO-meta cohort with seven independent GEO datasets of 519 BCa patients, and three immune checkpoint inhibitor (ICI)-treated cohorts. Considering the heterogeneity, re-clustering of iCAFs was performed and a subpopulation, named ""LOXL2+ iCAFs"", was identified. Co-culture CM derived from LOXL2 overexpression/silencing CAFs with T24 cells revealed that overexpression of LOXL2 in CAFs promoted while silencing LOXL2 inhibited the proliferation, migration, and invasion of T24 cells through IL32. Moreover, the positive correlation between LOXL2 and CD206, an M2 macrophage polarization marker, has been observed and validated. Collectively, integrated single-cell and bulk RNA sequencing analyses revealed an iCAF-related signature that can predict prognosis and response to immunotherapy for BCa. Additionally, the hub gene LOXL2 may serve as a promising target for BCa treatment."	bladder
Development and Internal Validation of a Nomogram Predicting Overall Survival Based on Log ODDS of Positive Lymph-Nodes for Post Radical Cystectomy Patients in Muscle Invasive Carcinoma of Bladder.	BACKGROUND: To develop and validate a nomogram based on LODDS (Log ODDS of positive lymph-nodes) for prediction of overall survival (OS) in post radical cystectomy (RC) patients of muscle invasive bladder cancer (MIBC). MATERIALS AND METHODS: Data was retrospectively collected from 282 cases of MIBC that underwent RC from 2011 to 2017 at our institute. Significant independent predictors were identified using Cox regression model and incorporated into a nomogram to predict 1, 2, and 4-year OS. RESULTS: Multivariate analysis showed that Neo-Adjuvant Chemo-Therapy (NACT) (P< .001), LODDS (P< .001), T-stage (Pi = .001), CCI (Charlson Comorbidity Index) (P = .034) and grade (P = .003) were independent predictors of OS. The C-index of nomogram (0.740) was higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.614). The bias-corrected calibration plots showed that the predicted risks were in excellent accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram. CONCLUSION: A simple, easy to use nomogram to predict OS in cases of MIBC has been constructed. To best of our knowledge, LODDS has been incorporated for the first time. It has superior predictive ability and higher clinical use than AJCC system. It would help the clinicians for better patient counselling, planning follow-up strategies and designing a clinical trial for newer adjuvant therapy (eg immunotherapy) in post radical cystectomy patients of MIBC.	bladder
Prognostic significance of minor high grade component in non-invasive papillary urothelial carcinoma of urinary bladder: (A study of 273 consecutive cases over a period of 3 years).	PURPOSE: Our study aimed to determine the prognostic significance of minor high-grade components (HGC) in non-invasive papillary urothelial carcinomas compared with pure low-grade and high-grade tumors. MATERIAL AND METHODS: We retrospectively retrieved 273 in-house cases of non-invasive papillary urothelial carcinomas (pTa) from 2016 to 2018 for which follow up data was available in hospital archives. We stratified our data into four main groups (G). G1, pure low-grade (n = 164); G2, HGC ≤5 % (n = 17); G3, HGC >5 % to ≤25 % (n = 14); and G4, pure high-grade (n = 78). Prognosis was assessed in terms of recurrence, grade and stage of progression, metastasis, and death. The mean follow up duration was 34.72 ± 20 months (range 20-60 months). RESULTS: All four groups showed no difference in tumor recurrence (G1 81.7 %, G2 88.2 %, G3 92.9 %, G4 92.3 % p-value 0.183). In terms of grade progression, there was no significant difference in G2 35.3 % and G3 35.7 % and both groups showed worst prognosis compared to G1 16.5 % p-value 0.04. Regarding stage progression (G1 6.7 %, G2 23.5 %, G3 28.6 %, G4 41% p-value 0.001), metastasis (G1 5.5 %, G2 5.9 %, G3 7.1 %, G4 17.9 % p-value 0.01) and death (G1 4.3 %, G2 5.9 %, G3 7.1 %, G4 15.4 % p-value 0.02) there was no significant difference in G2 and G3 and both groups showed worst prognosis than G1 and better than G4. CONCLUSION: Urothelial carcinomas with minor high-grade component ≤25 % behaved worst than pure low grade and better than pure high grade and should be treated as distinct grade entity.	bladder
A Phase I Study of the Non-Receptor Kinase Inhibitor Bosutinib in Combination with Pemetrexed in Patients with Selected Metastatic Solid Tumors.	"Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on ""standard of care"" chemotherapy were enrolled in a 3 + 3 dose escalation study. Oral Bosutinib was administered once daily beginning on day 1, where the first cohort started at an oral dose of 200 mg daily with pemetrexed 500 mg/m(2) IV on a three-week schedule. The study's primary objective was to determine the dose-limiting toxicity (DLT), the MTD of Bosutinib in combination with pemetrexed, and the type and frequency of adverse events associated with this treatment. Twelve patients were evaluable for response, including ten patients with adenocarcinoma of the lung, one patient with metastatic adenocarcinoma of the appendix, and one patient with urothelial carcinoma. The median number of Bosutinib and pemetrexed cycles received was 4 (range, 1-4). The MTD of oral Bosutinib in this combination was 300 mg daily. Two patients (17%) had a partial response (PR), and seven patients (58%) showed stable disease (SD) as the best response after the fourth cycle (end of treatment). One patient had disease progression after the second cycle, while three patients had disease progression after the fourth cycle. The two responders and the two patients with the longest stable disease duration or stabilization of disease following progression on multiple systemic therapies demonstrated Src overexpression on immunohistochemical staining of their tumor. The median progression-free survival (PFS) was 6.89 months (95% CI (3.48, 30.85)), and the median overall survival (OS) was 11.7 months (95% CI (3.87, 30.85)). Despite the limitations of this Phase I study, there appears to be potential efficacy of this combination in previously treated patients."	bladder
A case of undifferentiated carcinoma of the bladder treated by combination therapy of surgery, local radiation, and immune checkpoint inhibitors.	Undifferentiated carcinoma of the bladder is a rare malignancy with a poor prognosis. We present the case of an 81-year-old woman complaining of bladder irritation. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a bulky bladder tumor, which was diagnosed as cT4aN0M0. A transurethral resection of the bladder tumor revealed pT2 or higher urothelial carcinoma. The patient underwent total cystectomy with an ileal conduit diversion. Histological examination revealed a primary undifferentiated bladder carcinoma with a sarcoma component, pT3aN0M0. Postoperative adjuvant chemotherapy with gemcitabine plus carboplatin was administered. However, this regimen was discontinued after one course due to significant myelosuppression. Four months after total cystectomy, a pelvic tumor with suspected local recurrence was detected on CT. The patient was diagnosed with recurrent undifferentiated carcinoma with a sarcoma component by a transperineal ultrasound-guided biopsy. Local radiation therapy and immunotherapy with immune checkpoint inhibitors were prescribed. After three courses of immunotherapy with pembrolizumab, the primary tumor disappeared. Upon continuing immune checkpoint inhibitor treatment, the patient has maintained a complete response without tumor recurrence in the following six months.	bladder
Investigating PSMA differential expression in canine uroepithelial carcinomas to aid disease-based stratification and guide therapeutic selection.	BACKGROUND: In male dogs, uroepithelial cancers include invasive urothelial carcinoma (iUC) and prostate carcinoma (PCA). The inability to distinguish iUC involving the prostate from PCA results in indiscriminate clinical management strategies that could be suboptimal as first-line chemotherapy for iUC (cisplatin) and PCA (docetaxel) differ in people. Prostate specific membrane antigen (PSMA) is a transmembrane protein, and its overexpression has been identified in human prostate carcinoma and neovasculature associated with solid tumor growth. This study investigates whether differential PSMA expression exists between presumptive canine iUC and PCA among cell lines and archived patient samples, which might allow for improved accuracy in disease-based stratification and optimal chemotherapy selection. Additionally, in vitro sensitivities of reported canine iUC and PCA cell lines to uroepithelial directed chemotherapeutic agents were characterized. RESULTS: Normalized PSMA gene and protein expressions were not significantly different between 5 iUC and 4 PCA cell lines. PSMA protein expression was uniformly observed in uroepithelial cancers regardless of anatomic origin from archived patient samples, further confirming that PSMA cannot differentiate iUC from PCA. In vitro sensitivity of cell lines to uroepithelial directed chemotherapeutics revealed that vinblastine exerted the broadest cytotoxic activity. CONCLUSIONS: Differential expression of PSMA was not identified between canine iUC and PCA cell lines or archived patient samples, and PSMA alone cannot be used for disease stratification. Nonetheless given its conserved overexpression, PSMA may be a targetable surface marker for both canine iUC and PCA. Lastly, in uroepithelial carcinomas, vinblastine might exert the broadest anticancer activity regardless of cellular origin.	bladder
KLHL21/CYLD signaling confers aggressiveness in bladder cancer through inactivating NF-κB signaling.	Bladder carcinoma (BC) is one of the most commonly diagnosed malignant cancers worldwide. Kelch-like protein 21 (KLHL21) has been shown to be involved in a number of human tumors. The study aimed to investigate the effects and mechanism of KLHL21 on BC progression. We found that KLHL21 expression was significantly decreased in human BC tissues and cell lines compared with the paired normal samples, and patients with lower KLHL21 expression exhibited poorer overall survival. In vitro studies then showed that KLHL21 over-expression significantly reduced the proliferation, migration and invasion in BC cells, while KLHL21 knockdown markedly accelerated the proliferative, migratory and invasive properties of BC cells. Animal studies confirmed that KLHL21 exhibited anti-tumor function in the xenograft mouse models, as indicated by the reduced tumor growth rates, and mice with KLHL21 knockdown showed the opposite tumor growth profile. Additionally, we found that KLHL21 negatively mediated the nuclear factor-κB (NF-κB) signaling activation, as well as its down-streaming molecules involved in the biological regulation of cell survival, death and migratory processes. Mechanistically, cylindromatosis (CYLD) expression levels were significantly up-regulated in BC cells over-expressing KLHL21, but were down-regulated upon KLHL21 knockdown. We further uncovered that KLHL21 directly interacted with CYLD in BC cells. Of note, we found that KLHL21 mainly in cytoplasm could restrain CYLD degradation by prohibiting its ubiquitination in BC cells. More importantly, our in vitro experiments displayed that KLHL21-inhibited progression and NF-κB/p65 activation in BC cells were completely abolished by CYLD deletion, revealing that CYLD expression was required for KLHL21 to perform its anti-tumor function in BC. Collectively, all these findings uncovered that KLHL21/CYLD axis may be a promising therapeutic target for BC treatment.	bladder
Management of metastatic urothelial carcinoma: Current approach, emerging agents, and future perspectives.	Metastatic urothelial carcinoma (mUC) is a lethal disease for which platinum-based chemotherapy represents the standard of care; however, long-term survival is achieved only in a minority of patients. Recently, along with important advances in the comprehension of the biology of this disease, the treatment paradigm of mUC has undergone a rapid expansion with the approval of several immune-checkpoint inhibitors (ICIs) and targeted agents in both first- and second-line settings. Cisplatin-based chemotherapy remains the backbone of first-therapy for mUC; nevertheless, for those patients who do not progress after the full course of first-line chemotherapy, maintenance treatment with the anti-PD-L1 avelumab showed to prolong overall survival compared observation alone. Moreover, the disappointing results of chemotherapy in pre-treated patients have led to the investigation and the subsequent approval of the anti-PD-1 pembrolizumab, which showed an unprecedented survival benefit when compared to second-line chemotherapy. Recently, target therapy with the antibody-drug conjugate (ADC) enfortumab vedotin, directed against Nectin-4, showed outstanding results in patients treated with both chemotherapy and immunotherapy. The FGFR inhibitor erdafitinib and sacituzumab govitecan, an ADC targeting Trop-2, demonstrated encouraging activity in phase II studies and are currently under investigation in randomized phase III trials. ICIs and targeted therapies also demonstrated promising results as first-line treatment of cisplatin-ineligible patients; randomized trials of ICIs alone or in combination with targeted agents are ongoing and may broaden the therapeutic armamentarium for this category of patients. In this review, we describe the current state of art for the treatment of mUC; in addition, we present the latest evidences from the most recent literature and congress presentations. Finally, we illustrate the key ongoing clinical trials, focusing on ICIs and target therapies.	bladder
Kidney-sparing surgery for distal high-risk ureteral carcinoma: Clinical efficacy and preliminary experiences in 22 patients.	BACKGROUND: Several groups proved kidney-sparing surgery (KSS) had equivalent oncological outcomes compared with radical nephroureterectomy (RNU) for the low-risk upper urinary tract urothelial carcinoma (UTUC) patients. Whereas, the clinical efficacy of KSS for high-risk UTUC, especially for distal high-risk ureteral carcinoma, remains unclear. OBJECTIVE: To evaluate the feasibility of KSS for patients with distal high-risk ureter cancer. MATERIALS AND METHODS: Our study included 22 patients who diagnose the distal high-risk ureter cancer and underwent KSS between May 2012 and July 2021 in the First Affiliated Hospital of Chongqing Medical University. Overall survival (OS), confirmed as the primary endpoint of present study, was assessed by a blinded independent review committee (BIRC). The secondary endpoints included the postoperative SF-36 (the short form 36 health survey questionnaire) score, progression-free survival (PFS), postoperative complications, and so on. RESULTS: Overall, 17 (77.3%) and 5 (22.7%) patients underwent segmental ureterectomy (SU) and endoscopic ablation (EA), respectively. By the cut-off date, the mean OS was 76.3 months (95% Cl: 51.3-101.1 months) and the mean PFS was 47.0 months (95% Cl: 31.1-62.8 months), respectively. And the SF-36 score in a majority of patients was >300 (90.9%). CONCLUSION: This is a daring endeavor to explore the clinical efficacy of KSS in distal high-risk ureter cancer based on the high-risk UTUC criteria, which shows satisfactory results in the long-term prognosis and operation-associated outcomes. However, future randomized or prospective multicenter studies are necessary to validate our conclusions.	bladder
Systematic review of population-based bladder cancer registries: How criteria heterogeneity affects the comparison of incidences.	BACKGROUND: The population-based registry of bladder cancer (BC) raises specific problems intrinsic to the tumor, as the inclusion of noninfiltrating, potentially malignant and multiple tumors. We performed a systematic review (PRISMA guidelines) of population-based BC registries to obtain information on their geographic areas involved, last dates of real incidence of BC, and rules coding used in BC for uncertain behavior, in situ and multiple tumors. METHODS: Using MEDLINE and Google Scholar, we identified scientific publications of in the last 10 years in English or Spanish, whether they were related to a national or international cancer registry, provided information on registry rules, and provided data on the incidence of BC. RESULTS: After the first screening, a total of 194 references were obtained. After a second analysis, three registries were selected: International Agency for Research on Cancer (IARC) is a world registry providing real incidence of BC in the period 2008-2012. Surveillance, Epidemiology, and End Results (SEER) Program registered incidence until 2017 in more than 90% of the US population. Spanish Network of Cancer Registries (REDECAN) unifies 14 Spanish registries (27.4% of the population) with real incidence data from 2010 to 2015. The coding and inclusion rules have been modified, but currently, most registries include BC in situ and uncertain behavior tumors. Whenever a new case occurs 36 months after a previous diagnosis, SEER registers those as multiple incident cancers in the same location, while IARC and REDECAN only allow one cancer per location during the lifespan of the patient. CONCLUSIONS: Comparison of the incidence of BC among different population-based cancer registries is prone to bias due to the methodological differences regarding the inclusion of carcinomas in situ, indeterminate, and multiple tumors. A good cancer registry could provide better surveillance strategies for BC patients.	bladder
Robotic-assisted Versus Laparoscopic Versus Open Radical Cystectomy-A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.	CONTEXT: Multiple randomized controlled trials (RCTs) on the three approaches of radical cystectomy (robotic assisted [RARC], laparoscopic [LRC], and open [ORC]) have been published recently. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) of RCTs comparing RARC, LRC, and ORC, with the primary outcomes being overall survival (OS) and recurrence-free survival (RFS). EVIDENCE ACQUISITION: A search of the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science (last search: 20/05/2022) was performed. The prospectively registered protocol stated that a NMA of the primary outcomes would be performed only if there was sufficient evidence to compare all three approaches. In case of insufficient evidence, a comparison between the two most common approaches would be performed. The risk of bias and certainty of evidence (CoE) via the Grading of Recommendations Assessment, Development, and Evaluation approach was assessed for direct evidence and the most common comparison. EVIDENCE SYNTHESIS: Ten trials were identified. There was insufficient evidence for a NMA of all approaches for the primary outcomes. The meta-analysis of RARC and ORC showed no differences in OS (hazard ratio (HR) [confidence interval (CI): 0.98 [0.73-1.30]) and RFS (HR [CI]: 0.99 [0.75-1.31]) with moderate CoE. The secondary outcomes showed lower rates of transfusions (p < 0.01) and longer operating time (p < 0.01) with high CoE for RARC compared with ORC. There were no differences for quality of life, positive margins, length of hospital stay, or major complications (all p > 0.05). CONCLUSIONS: There are no differences in OS and RFS between RARC and ORC, with moderate CoE. Clinicians should likely apply the approach with which they can reach the highest case volume and in which they have the most experience. PATIENT SUMMARY: We looked at the difference between three types (robotic assisted, laparoscopic, and open) of operating techniques for radical cystectomy. The data showed no significant differences in OS between the robotic-assisted and the open technique, while enough data were not available to make a comparison with conventional laparoscopic surgery.	bladder